A real-word prospective study of anti-amyloid treatment in a single-center memory clinic: a six month experience

Background: Anti-amyloid monoclonal antibodies are emerging as disease-modifying treatments for early Alzheimer’s disease (AD), showing substantial efficacy in reducing cerebral amyloid burden and slowing cognitive and functional decline in clinical trials. However, Italian real-world evidence on feasibility, safety and implementation of such therapy in the health services are still limited. Objectives: The objective of this study is to delineate the multidisciplinary diagnostic pathway developed to assess patient eligibility for anti-amyloid therapy (AAT) within a tertiary memory clinic, highlighting the main determinants of patient exclusion. Additionally, the study aims to provide preliminary real-world safety data and to propose a structured model for the implementation of AAT into routine clinical practice. Methods: This prospective observational study at the Memory Clinic, University Hospital of Padua enrolled patients with a diagnosis of possible/probable Alzheimer’s disease (AD) without exclusion criteria for AAT after first-level assessment (clinical, cognitive and MRI study) and with second-level biomarker validation (CSF and/or Amyloid PET). Candidates were evaluated by a structured multidisciplinary team (neurologists, neuroradiologists, nuclear medicine physicians, psychologists, clinical coordinator). Brain MRI (including GRE and SWI sequences) and amyloid-PET with early acquisition images were revised. The study covers the first six-month implementation period (Nov 1, 2025–Apr 30, 2026). Results: The initially screened cohort included 53 patients (mean age 65.9 years; mean MMSE 23). Following eligibility assessment, 33 patients were excluded, 3 are currently under evaluation, and 17 were considered eligible. Among excluded patients, the main reasons were significant cerebrovascular disease (n=13, 39.4%), disease severity (n=8, 24.2%), non-AD neurodegenerative overlap including frontotemporal spectrum disorders (n=8, 24.2%). Genetic screening (n=43) revealed one APOE ε4/ε4 homozygote and one patient presenting a pathogenic PSEN1 mutation. Biomarker discordance between CSF and amyloid-PET was observed in 11 out of 35 patients (31.4%), including one APOE ε2/ε3 carrier with A+ T+ CSF but negative PET, and 10 patients with A+ T- or borderline CSF profiles (7 PET-positive, 3 PET-negative). Two patients with CSF A+T- had a discordant AD staging and an associated neurodegenerative comorbidity was found (DLB and LATE). These patients were deemed not eligible. Conclusions: In a real-world tertiary memory clinic setting, six-month implementation of AAT treatment was feasible and efficient. Major limiting factors for eligibility included presence of subtle cerebrovascular disease, advanced disease stage and non-AD neurodegenerative conditions. These findings support structured pathways for anti-amyloid therapy implementation in European memory clinics.